dermatologia

Frequent skin cancers due to mutations in genes responsible for repairing DNA are linked to a threefold risk of unrelated cancers, according to a Stanford study. The finding could help identify people for more vigilant screening.

Basal cell carcinomas are common. More than 3 million cases a year are diagnosed nationwide.jax10289/Shutterstock.com

People who develop abnormally frequent cases of a skin cancer known as basal cell carcinoma appear to be at significantly increased risk for developing of other cancers, including blood, breast, colon and prostate cancers, according to a preliminary study by researchers at the Stanford University School of Medicine.

The increased susceptibility is likely caused by mutations in a panel of proteins responsible for repairing DNA damage, the researchers found.

“We discovered that people who develop six or more basal cell carcinomas during a 10-year period are about three times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, assistant professor of dermatology. “We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

Sarin is the senior author of the study, which was published online Aug. 9 in JCI Insight. Medical student Hyunje Cho is the lead author.

Largest organ

The skin is the largest organ of the body and the most vulnerable to DNA damage caused by the sun’s ultraviolet rays. Try as one might, it’s just not possible to completely avoid sun exposure, which is why proteins that repair DNA damage are important to prevent skin cancers like basal cell carcinoma.

Kavita Sarin

Most of the time this system works well. But sometimes the repair team can’t keep up. Basal cell carcinomas are common — more than 3 million cases a year are diagnosed in the United States alone — and usually highly treatable.

Sarin and Cho wondered whether the skin could serve as a kind of canary in the coal mine to reveal an individual’s overall cancer susceptibility. “The skin is basically a walking mutagenesis experiment,” Sarin said. “It’s the best organ to detect genetic problems that could lead to cancers.”

Sarin and Cho studied 61 people treated at Stanford Health Care for unusually frequent basal cell carcinomas — an average of 11 per patient over a 10-year period. They investigated whether these people may have mutations in 29 genes that code for DNA-damage-repair proteins.

“We found that about 20 percent of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3 percent of the general population. That’s shockingly high,” Sarin said.

Furthermore, 21 of the 61 people reported a history of additional cancers, including blood cancer, melanoma, prostate cancer, breast cancer and colon cancer — a prevalence that suggests the frequent basal cell carcinoma patients are three times more likely than the general population to develop cancers.

‘A strong correlation’

To confirm the findings, the researchers applied a similar analysis to a large medical insurance claims database. Over 13,000 people in the database had six or more basal cell carcinomas; these people also were over three times more likely to have developed other cancers, including colon, melanoma and blood cancers. Finally, the researchers identified an upward trend: the more basal cell carcinomas an individual reported, the more likely that person was to have had other cancers as well.

“I was surprised to see such a strong correlation,” Sarin said. “But it’s also very gratifying. Now we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers, and perhaps suggest that they consider genetic testing and increased screening.”

The researchers are continuing to enroll Stanford patients in the study, which is ongoing, to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. They’d also like to conduct a similar study in patients with frequent melanomas. But they emphasized that there’s no reason for people with occasional basal cell carcinomas to worry.

“About 1 in 3 Caucasians will develop basal cell carcinoma at some point in their lifetime,” Sarin said. “That doesn’t mean that you have an increased risk of other cancers. If, however, you’ve been diagnosed with several basal cell carcinomas within a few years, you may want to speak with your doctor about whether you should undergo increased or more intensive cancer screening.”

Synchronous balneo-phototherapy, in which a Dead Sea salt bath is used simultaneously with ultraviolet light therapy, could be beneficial for treating atopic eczema, according to the German Institute for Quality and Efficiency in Health Care (IQWiG).

The IQWiG had previously determined a greater benefit of balneo-phototherapy than phototherapy alone in psoriasis, but at that time said convincing results were not available for atopic eczema.

As part of a new review of evidence, commissioned by the Federal Joint Committee in Germany, the IQWiG considered findings from two studies. The first study included 180 patients while the second included 500 people with atopic eczema who were treated for at least one month, and received between 10 and 35 treatment sessions.

The IQWiG noted that results for the outcome “skin status”, which included symptoms such as itching or insomnia, were in favour of synchronous balneo-phototherapy. However, the review did not reach conclusions on quality of life or side effects.

Stefan Sauerland, Head of the IQWiG Department of Non-Drug Interventions, said high-quality studies on bathing treatments are important to be able to “separate the useful from the useless” in the management of atopic eczema.

The conjunctiva (the membrane that lines the eyelid and covers the white of the eye) contains a large number of cells from the immune system (called mast cells) that release chemical substances (called mediators) in response to a variety of stimuli (such as pollens, mold spores, or dust mites). These mediators cause inflammation in the eyes, which may be brief or long-lasting. About 20% of people have some degree of allergic conjunctivitis.

An Inside Look at the Eye

Seasonal allergic conjunctivitis (hay fever conjunctivitis) and year-round or perennial allergic conjunctivitis (atopic conjunctivitis, atopic keratoconjunctivitis) are the most common types of allergic reaction in the eyes. Seasonal allergic conjunctivitis is often caused by mold spores or tree, weed, or grass pollens, leading to its typical appearance in the spring and early summer. Weed pollens are responsible for symptoms of allergic conjunctivitis in the summer and early fall. Perennial allergic conjunctivitis occurs year-round and is most often caused by dust mites or animal dander.

Vernal keratoconjunctivitis is a more serious form of allergic conjunctivitis in which the stimulant (allergen) is not known. The condition is most common among boys, particularly those aged 5 to 20 years who also have eczema, asthma, or seasonal allergies. Vernal keratoconjunctivitis typically reappears each spring and subsides in the fall and winter. Many children outgrow the condition by early adulthood.

Symptoms

People with all forms of allergic conjunctivitis develop intense itching and burning in both eyes. Although symptoms usually affect both eyes equally, rarely one eye may be more affected than the other. The conjunctiva becomes red and sometimes swells, giving the surface of the eyeball a puffy appearance. The eyelids may become intensely itchy. Rubbing and scratching leads to eyelid skin redness, swelling, and a crinkly appearance.

With seasonal allergic conjunctivitis and perennial allergic conjunctivitis, there is a large amount of thin, watery discharge. At times the discharge is stringy. Vision is seldom affected. Many people have an itchy, runny nose.

With vernal keratoconjunctivitis, the eye discharge is thick, stringy, and mucuslike. Unlike other types of allergic conjunctivitis, vernal keratoconjunctivitis often affects the cornea (the clear layer in front of the iris and pupil), and in some people painful, small, open sores (corneal ulcers) develop. These ulcers cause deep eye pain with exposure to bright light (photophobia) and sometimes lead to a permanent decrease in vision.

Diagnosis

A doctor’s evaluation of the symptoms and appearance of the eye

Doctors recognize allergic conjunctivitis by its typical appearance and symptoms. Tests are rarely needed or useful.

Treatment

Eye drops and tear supplements

Allergic conjunctivitis treatment includes anti-allergy eye drops. Using chilled tear supplements and cold compresses and avoiding known allergens can help reduce symptoms.

Drops that have an antihistamine, such as ketotifen, may be enough for mild cases. This drug can be bought without a prescription. If ketotifen is insufficient, prescription antihistamine eye drops (such as olopatadine) or mast cell stabilizers (such as nedocromil) may be effective.

Nonsteroidal anti-inflammatory eye drops, such as ketorolac, help relieve symptoms. Corticosteroid eye drops have more potent anti-inflammatory effects. However, these eye drops should not be used for more than a few weeks without close monitoring by an ophthalmologist (a medical doctor who specializes in the evaluation and treatment [surgical and nonsurgical] of eye disorders) because they may cause increased pressure in the eyes (glaucoma), cataracts, and an increased risk of eye infections.

Antihistamines taken by mouth, such as fexofenadine, cetirizine, or hydroxyzine, may also be very helpful, especially when other areas of the body (eg, ears, nose, throat) are affected by the allergies.